BACKGROUND: Current standard treatment for metastatic breast cancer (MBC) involves cyclin-dependent kinase 4/6 (CDK4/6) inhibitors with endocrine therapy, showing potential in enhancing anti-tumor immune responses.
METHODS: This report details a clinical case of MBC where palbociclib was co-administered with letrozole. The integration of allogeneic tumor vaccination to this treatment led to heightened interferon-γ production, expansion of CD8+ and NK cell populations, and positive delayed-type hypersensitivity reactions, indicating successful development of anti-tumor immunity. The induced production of interferon-γ by tumor vaccination was associated with manageable modulation of sensitivity to palbociclib-letrozole therapy. Administration of the BioNTech/Pfizer Covid-19 vaccine compromised the anti-tumor immune response by reducing cytotoxic cell populations and increasing immunosuppressive cytokine production. The patient undergoing combined treatment achieved a progressive-free survival of 42 months.
CONCLUSIONS: Incorporating active tumor vaccination with CDK4/6 inhibitor therapy presents a feasible approach for metastatic breast cancer. The precise regulation of the microenvironment emerges as a crucial factor and warrants careful consideration.

A precisely designed dual-color biosensor has realized a visual assessment of thymidine kinase 1 (TK1) mRNA in both living cells and cell lysates. The oligonucleotide probe is constructed by hybridizing the antisense strand of the target and two recognition sequences, in which FAM serves as the donor and TAMRA as the acceptor. Once interacting with the target, two recognition strands are replaced, and then the antisense complementary sequence forms a more stable double-stranded structure. Due to the increasing spatial distance between two dyes, the FRET is attenuated, leading to a rapid recovery of FAM fluorescence and a reduction of TAMRA fluorescence. A discernible color response from orange to green could be observed by the naked eye, with a limit of detection (LOD) of 0.38 nM and 5.22 nM for spectrometer- and smartphone-based assays, respectively. The proposed ratiometric method transcends previous reports in its capacities in visualizing TK1 expression toward reliable nucleic acid biomarker analysis, which might establish a general strategy for ratiometric biosensing via strand displacement.

Thymidine kinase 1 (TK1) is a marker of cell proliferation that can be used for early screening, treatment monitoring, and evaluating the prognosis of patients with tumors. The main purpose of this study was to develop clinically applicable TK1 antibodies, establish an appropriate detection method, and provide material and technical support for the research and clinical application for different types of tumors. Experimental mice were immunized with the C-terminal 31 peptide of human TK1 to screen monoclonal cell lines capable of stably secreting specific antibodies. Monoclonal antibodies were then prepared, purified and screened for optimal pairing following the identification of purity and isotype. Finally, based on the principles adopted by the double-antibody sandwich detection method, we constructed a lateral flow immunochromatographic assay (LFIA) to quantify the concentration of TK1 in serum samples when using a gold nanoparticle-labeled anti-TK1 monoclonal antibody as a probe. The limit of detection for TK1 in serum was 0.31 pmol/L with a detection range of 0.31-50 pmol/L. The spiked recoveries ranged from 97.7% to 109.0% with an analytical precision of 5.7-8.2%; there was no cross-reactivity with common proteins in the serum. The established LFIA also exhibited good consistency with commercially available chemiluminescent immunoassay kits for the detection of clinical samples. The LFIA developed in this study has the advantages of high sensitivity, accuracy, reproducibility and strong specificity, and provides a new technical tool for the quantitative detection of TK1.

UNASSIGNED: Construction of a nomogram model based on Thymidine kinase 1 (TK1) in combination with inflammatory indicators and tumor markers to predict the probability of recurrence in mid- to late-stage cervical cancer.
UNASSIGNED: One hundred fourteen instances of intermediate and advanced cervical cancer admitted to our hospital\'s radiotherapy department between June 2017 and January 2023 were retrospectively studied. Logistic regression analysis includes variables relevant for univariate analysis. Meaningful indications from multifactor analysis were included in the nomogram model, the model\'s correctness was evaluated using the C-index, and the model\'s effectiveness was assessed using calibration curves, clinical decision curves, and clinical impact curves.
UNASSIGNED: A nomogram model was created due to the logit regression analysis that revealed the squamous cell carcinoma antigen (SCC) and TK1 as independent recurrence predictors following cervical cancer radiation (P<0.05). The C index and Area Under the Curve (AUC) were 0.79 (95% CI 0.67-0.91). The AUC and C-index were both more extraordinary than those of TNM staging alone (C-index 0.57, 95% CI 0.43-0.71) and SCC alone (C-index 0.67, 95% CI 0.51-0.82). Calibration curves, Decision Curve Analysis (DCA), and clinical impact curves (CIC) indicate that the model predicts probabilities more accurately.
UNASSIGNED: The nomogram model based on TK1 combined with inflammatory markers and tumor markers is more reliable than the TNM staging and SCC systems alone for forecasting recurrence after radiotherapy in intermediate- and advanced-stage cervical cancer. It is also a cheap, practical, and simple-to-obtain model that can supplement the TNM staging system for forecasting prognosis and significantly enhances clinicians\' decision-making.

OBJECTIVE: To search for new predictive breast cancer biomarkers. We analyzed the serum concentrations of biomarkers involved in carcinogenesis, which can also be targeted by therapy.
METHODS: In a single-center prospective study, the serum levels of Aurora A, thymidine kinase 1, and human epidermal growth factor receptor type 3 (HER3) were determined in 119 women with BC before neoadjuvant treatment using ELISA kits.
RESULTS: The following clinical data were analyzed: age; TNM; the expression of ER, PGR, HER2, and Ki67; histological grade (G); and the response to neoadjuvant treatment (NAT) in the residual tumor burden classification (RCB). A complete pathological response (pCR) was achieved after NAT in 41 patients (34%). The highest proportion of the patients with a confirmed pCR was found for triple negative breast cancer (TNBC) (62.5%); non-luminal HER2-positive (52.6%) cancer subtypes (p = 0.0003); and in the G3 group (50%; p = 0.0078). The patients with higher levels of Aurora A were more likely to achieve pCR (p = 0.039). In the multivariate analysis, the serum Aurora A levels ≥ 4.75 ng/mL correlated with a higher rate of pCR (OR: 3.5; 95% CI: 1.2-10.1; p = 0.023).
CONCLUSIONS: We showed that in a biologically heterogeneous group of BC patients, the pretreatment serum Aurora A levels were of significant value in predicting the response to NAT.

Thymidine kinase 1 (TK1) level is an independent survival prognostic factor for both premalignant and malignant cervical pathologies. Herein, this study sought to probe the impacts of TK1 on cervical cancer (CC) progression and its underlying mechanism. Transcription factor Dp-1 (TFDP1) and TK1 expression was assessed using qRT-PCR in CC cell lines. After ectopic expression and knockdown experiments, cell counting kit-8 and colony formation assays were adopted to measure cell proliferation, western blot to examine the expression of epithelial-mesenchymal transition (EMT)-related proteins, and Transwell assays to assess cell invasion and migration. The binding of TFDP1 to TK1 was predicted by bioinformatic sites and verified by chromatin immunoprecipitation and dual-luciferase reporter assays. Tumor xenograft experiments in nude mice were performed to validate the influence of TFDP1/TK1 on CC progression in vivo. CC cells had high TK1 and TFDP1 expression. TFDP1 or TK1 knockdown restrained CC cell EMT, invasion, migration, and proliferation. TFDP1 facilitated TK1 expression in CC via transcription. Overexpression of TK1 counteracted the suppressive impacts of TFDP1 knockdown on CC cell malignant behaviors. Moreover, TFDP1 knockdown depressed CC growth in vivo by downregulating TK1. TFDP1 knockdown restricted proliferation and EMT in CC by downregulating TK1 expression.

BACKGROUND: Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer.
METHODS: The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples.
RESULTS: The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis.
CONCLUSIONS: These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer.

BACKGROUND: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) levels in hepatocellular carcinoma (HCC) prognosis and to develop a nomogram for predicting HCC prognosis.
METHODS: In this study, 1066 HCC patients were enrolled between August 2018 and April 2022. TK1 levels were measured within one week before enrollment, and the relationship with HCC prognosis was evaluated. Next, all patients were randomly assigned to the training set (70%, n = 746) and the validation set (30%, n = 320). We used multivariate Cox analysis to find independent prognostic factors in the training set to construct a nomogram. The predictive power of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The optimal critical value of TK1 was determined as 2.35 U/L using X-tile software.
RESULTS: Before and after propensity score matching (PSM), the median overall survival (mOS) of the low-TK1 group (< 2.35 U/L) remained significantly longer than that of the high-TK1 group (≥ 2.35 U/L) (48.1 vs 16.5 months, p < 0.001; 75.7 vs 19.8 months, p = 0.001). Moreover, multivariate Cox analysis showed that the low TK1 level was an independent positive prognostic indicator. Additionally, the area under the ROC curve for predicting the 1-year, 2-year, and 3-year survival rates was 0.770, 0.758, and 0.805, respectively.
CONCLUSIONS: TK1 could serve as a prognostic marker for HCC. In addition, the nomogram showed good predictive capability for HCC prognosis.

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988-1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.

OBJECTIVE: Serum thymidine kinase 1 (STK1) is a proliferation biomarker that has been used as a diagnostic marker of several malignant diseases. However, there are limited data for prostate cancer (PCa).
METHODS: In this study, we retrospectively analysed serum samples from 169 patients with biopsy confirmed PCa, who had been indicated for radical prostatectomy (RP) between 2013-2016. The results were compared with those in serum samples from 39 healthy men. We used commercially available enzymatic immunoassay to determine the levels of STK1. The patients were divided into groups according to the Gleason score (GS) and risk factors for adjuvant radiotherapy (aRT), which were defined as GS 8-10, pT3, and a positive surgical margin.
RESULTS: The median serum level of STK1 in PCa patients was 0.289 pmol/l. In the control group, the median value was 0.0116 pmol/l (p<0.001). By comparing the patients with GS≤6 vs. 7 vs. ≥8 (p=0.01), we found statistically significant differences. In the correlation of STK1 values with risk factors, we found statistically significant differences both in comparison of 0 vs. 1 vs. 2 vs. 3 risk factors (p=0.021), as well as ≤1 vs. 2≥ risk factors (p=0.009).
CONCLUSIONS: The levels of STK1 are significantly higher in patients with PCa than those in healthy controls. Furthermore, STK1 values correlate with GS and predefined risk factors for aRT. Therefore, STK1 can be considered as a potential tumour marker of PCa diagnosis and risk stratification.